Medicinal azo compounds



Patented Feb. 18, 1936 UNITEE STATES MEDICINAL AZO COMPOUNDS Raemer RexRenshaw, New York, and Edmond T. Tisza and Bernard F. Duesel, Yonkers,N. Y., assignors to The Pyridium Corporation, Nepera Park, N. Y., acorporation of New York No Drawing. Application March 28, 1932, SerialNo. 601,712

4 Claims.

This invention relates to medicinal preparations and also relates toprocesses for making the same.

Although many amino aromatic compounds and their derivatives are knownto have physiological action, they are generally not used for medicinalor therapeutic purposes, because of their toxicity, and also becausethey are oxidizable in the human body to para-hydroxyl derivatives.These para-hydroxyl derivatives, even though of decreased toxicity, andeven though they retain in large part the physiological action of thecompounds from which they were derived, do not function satisfactorilybecause of the activity of the para-hydroxyl grouping. These phenolichydroxyl groups readily enter into combinations including sulfonic orglucuronic acid groupings, which are inert and ineffective from aphysiological viewpoint.

For example, it was early found that compounds such as aniline andacetanilide (Schmiedeberg, Archiv. fur experimentelle Pathologie andPharmakologie, vol 8, page 1, 1878) are oxidized to para-amino phenolsin the human system, which last-mentioned compounds are eliminated fromthe system in the form of inert and ineffective combinations.

It has long been thought necessary, in order to decrease the toxicityand also to prevent the formation of such para-hydroxylated compounds,to insert a substituent group in the para-position in suchamino-aromatic derivatives. According to this theory, phenacetin and alarge number of other para compounds have been developed and haveachieved wide-spread utilization in the field of medicine.

We have now found, however, that it is possible to obtain certainorthoand/or meta-substituted azotized aromatic amines of markedlydecreased toxicity and enhanced therapeutic value, without regard towhether or not the paragroup was substituted.

These amines are preferably produced by the diazotization and couplingof a metaand/or ortho-substituted aromatic amine with a diamino aromaticcompound, such as meta-phenylenediamine. The preferred substituentsinclude alkyl and an alkoxy or hydroxy group. It is desirable to excludecertain substituent groups such as the sulphonic acid group from thesecompounds.

These compounds are not particularly toxic; whether or not they aresubstituted in the para position; are not converted into inert compoundseven though they may contain hydroxyl groups; and are particularly ofvalue because of their enhanced bactericidal action, and because oftheir elimination in the urine.

The probable structural formula of the preferred type of the metaand/ orortho-substituted azo compounds of the present invention is as followsILIHB R in which one of the groups R and R. represents an alkyl group,as for example, CH3 C2H5, C4H9,

C5H11, and so forth, and the other rep-resents an alkoxy group, as forexample, OCH3, OCzHs,

OC5H11, or a hydroxy group.

The preferred method of obtaining these compounds is by diazotizing thecorresponding orthoand/ormeta-substituted anilin and coupling thecorresponding diazonium salt with m-p-henylendiamine in acid solution.

The dyes obtained are of similar character, and form from yellow to darkbrown crystals, faintly soluble in water, very soluble in organicsolvents such as methanol, ether, acetone, carbon tetrachloride, andtoluene. For purification, they may be recrystallized out of toluene.

With acids, they form salts, the hydrochlorides being dark red to bluishviolet colored crystals. These salts are soluble in water, from whichsolution the bases may be precipitated with an alkali. The hydroxide,carbonate, or acetate of the alkali may be used as the alkali for thispurpose.

With concentrated hydrochloric acid they also form a dihydrochloride,which is usually darker than the corresponding mono-hydrochloride.

The following examples illustrate various methods of obtaining somerepresentative medicinal preparations of the present invention.Equimolecular quantities were used of the compounds, which were coupledtogether toform the azo-derivative.

Example 1 2-methoxy-5-methyl-2', 4'-diamino-azobenzene.

Example 2 3.9 g. of 2-methyl4hydroxyaniline were dissolved in 120 cc. ofwater and 7.5 of concentrated hydrochloric acid. The solution was cooledto 4 C. and then diazotized with a 10% solution of sodium nitrite, usingpotassium iodide-starch paper as indicator to determine the end point.To this diazonium salt solution, a solution of 4.6 g.

of m-phenylenediamine hydrochloride in 20 cc.

of water was added. Upon making the solution almost neutral, copulationensued. Upon the adcould not be recrystallized from these solvents.

On the other hand it was so slightly soluble in toluene, ligroin orchloroform that these solvents cannot readily be employed. Therefore itis most satisfactorily produced as the hydrochloride.

The probable structural formula of this compound is:-

111E: 6H; Z-methyl--hydroxy-Z', 4'-diamino azobenzene.

What is claimed is: 1. As a new chemical monoazo compound useful formedicinal purposes. a di-amino-phenylsubstituents, at least one of whichis in orthoposition to the azo linkage, and at least one ofwhich'consists of a methyl group and the other of which is selected fromthe group consisting of methoxy and hydroxy.

2. A new chemical compound useful for medicinal purposes comprising anazo-benzene in which two nuclear hydrogen atoms are replaced byunsubstituted amino groups, another nuclear hydrogen atom is replaced bya lower alkyl group and still another is replaced by a lower alkoxygroup, in which the lower alkoxy and the lower alky contain the samenumber of. carbon atoms and are attached to onephenyl nucleus while theamino groups are attached to the other phenyl nucleus.

3. A new chemical compound useful for medicinal purposes comprising 2,4-diamino, 2- methoxy, 5 methyl-azo-benzene.

4. A new chemical compound useful for medicinal purposes comprising 2,4'-diamino, 2- methyl, 4-hydroxy azobenozene.

RAEMER REX REN'SHAW. EDMOND T. TISZA. BERNARD F. DUESEL.

